Commercialization of a Novel Therapeutic for Alzheimer's Disease

阿尔茨海默病新疗法的商业化

基本信息

批准号：
9253568
负责人：
MARK Anthony LOVELL
金额：
$ 50.86万
依托单位：
COPLEX THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-30 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9253568
关键词：
APP-PS1 Abeta synthesis Adrenal Glands Adverse effects Age Alzheimer&apos s Disease Alzheimer&apos s disease model Amyloid beta-Protein Anti-Inflammatory Agents Anti-inflammatory Autopsy Biological Availability Blood specimen Body Weight Brain Chromosome abnormality Clinical Clinical Chemistry Clinical Pathology Clinical Services Clinical Trials Collaborations Data Deposition Development Diet Disease Dose Drug Kinetics Female Formic Acids Future Guidelines Hematology High Pressure Liquid Chromatography Histopathology In Vitro Inflammatory Intestines Intravenous Isotope Labeling Kentucky Kidney Learning Legal patent Liver Maximum Tolerated Dose Mediating Memory Methods Modeling Mono-S Mus Mutation Naphthyridines Oral Outcome Pancreas Pathogenesis Pathogenicity Pathologic Pathology Pathway interactions Pharmaceutical Preparations Pharmacologic Substance Pharmacology Pharmacology and Toxicology Phase Phenotype Positioning Attribute Presenile Alzheimer Dementia Prevention Production Proteins Radial Rattus Recovery Regimen Risk Rivers Role Safety Series Spleen Sprague-Dawley Rats Tail Testing Therapeutic Time Toxic effect Toxicokinetics Toxicology Transcription Repressor/Corepressor Treatment Protocols Universities Veins Water amyloid formation animal resource arm base behavior measurement carboxylate commercialization cytokine drug development drug efficacy efficacy testing familial Alzheimer disease food consumption gamma secretase gene repression improved in vivo inhibitor/antagonist male mouse model mutant neuroinflammation notch protein novel novel therapeutics object recognition pre-clinical presenilin-1 presenilin-2 respiratory small molecule therapeutic target

项目摘要

ABSTRACT Traditional mon-therapeutic, target driven approaches to drug development for Alzheimer’s disease (AD) are becoming increasingly expensive and in many cases disappointingly unsuccessful. Based on preliminary in vitro and in vivo studies we have identified a novel small molecule (methyl 2,4-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridine-1-carboxylate; (BNC-1)) that significantly decreases neuroinflammation and production of Aβ42 in mouse models of AD pathology through Elk-1 mediated transcriptional repression of presenilin-1 but not presenilin-2. Although our preliminary data show BNC-1 effectively modulates 2 of the main pathologic features of AD without the adverse effects associated with current mono- therapeutics, there is a need for characterization of its basic pharmacology/toxicity and for identification of the most efficacious treatment regimen in a well characterized mouse model of Aβ deposition and neuroinflammation (5X FAD mice). If successful, the data obtained in this proposal will provide necessary pharmacology/safety toxicology data to de-risk the drug for potential corporate partners thus increasing the likelihood of successful commercialization.

抽象的传统的Mon治疗，目标驱动的阿尔茨海默氏症药物开发方法疾病（AD）变得越来越昂贵，在许多情况下令人失望不成功。基于初步的体外和体内研究，我们已经确定了一个新颖的小型分子（甲基2,4-二甲基-5-oxo-5,6-二氢苯并[C] [2,7]萘胺-1-羧酸萘酯；（BNC-1））显着降低了小鼠中Aβ42的神经炎症和产生通过ELK-1介导的Presenilin-1的转录表示AD病理的模型，但不是Presenilin-2。尽管我们的初步数据显示BNC-1有效调节主要的2 AD的病理特征，没有与当前单声道相关的不良反应治疗，需要表征其基本药理学/毒性和鉴定最有效的治疗方案在特征良好的小鼠模型中 Aβ沉积和神经炎症（5x FAD小鼠）。如果成功，则在此获得的数据提案将提供必要的药理学/安全毒理学数据，以降低风险的药物潜在的公司合作伙伴增加了成功商业化的可能性。